Featured Research

from universities, journals, and other organizations

Researcher Hits Bulls-eye For Antibiotic Target

Date:

August 22, 2006

Source:

Purdue University

Summary:

A Purdue University researcher has opened the door for possible antibiotic treatments for a variety of diseases by determining the structure of a protein that controls the starvation response of E. coli. This research is applicable to the treatment of many diseases because that same protein is found in numerous harmful bacteria.

Share This

A surface representation of exopolyphosphatase, a protein with great potential as an antibiotic target. David Sanders, an associate professor of biology, determined the structure using X-ray crystallography and discovered unique features. The protein is involved in the starvation response of E. coli. (Graphic: Sanders Lab)

A Purdue University researcher has opened the door for possible antibiotic treatments for a variety of diseases by determining the structure of a protein that controls the starvation response of E. coli.

Related Articles

This research is applicable to the treatment of many diseases because that same protein is found in numerous harmful bacteria, including those that cause ulcers, leprosy, food poisoning, whooping cough, meningitis, sexually transmitted diseases, respiratory infections and stomach cancer, said David Sanders, an associate professor of biology. Sanders, who is part of the Markey Center for Structural Biology at Purdue, detailed his research in a paper published in the Aug. 16 issue of the journal Structure.

"This is an important discovery for the field of antibiotics, which was greatly in need of something new," Sanders said. "The antibiotics available today face a challenge of increasing resistance and failure. This research suggests a whole new approach to combat bacterial infections. In addition, this protein is an excellent antibiotic target because it only exists in bacteria and some plants, which means the treatment will only affect the targeted bacterial cells and will be harmless to human cells."

Sanders and his collaborator, Miriam Hasson, studied the structure of exopolyphosphatase, a protein in E. coli bacteria that functions as an enzyme and catalyzes chemical reactions within the bacteria. This enzyme provides the signal for bacteria to enter starvation mode and limit reproduction.

"With the ability to control the use of this signal, we can fool bacteria into thinking they are starving all the time, even when they are not; or we could never allow them to realize that they're starving, and that would kill them as well."

Researchers could design drugs to bind to the protein and keep it from being used by the bacteria, rendering the bacteria unable to react to and survive a lack of nutrient supply; the other possibility would be to design a drug to mimic the protein, causing the bacteria to react as if it were starving even when in the presence of a plentiful nutrient supply, Sanders said.

Such a signal exists in almost all living things because most organisms struggle to find food or nutrients and have had to develop a way to avoid starvation, he said.

"Bacteria typically are in an environment lacking nutrients and respond by limiting their reproduction," he said. "And that's a good thing because if they were growing at their maximum rate all the time, within two weeks we would be 20 feet deep in bacteria."

The protein also is of particular interest because it is highly processive, meaning it is efficient in the chemical reaction it initiates. It is able to latch onto its substrate, the substance it uses to fuel its chemical reaction, and to stay tenaciously in place until it has consumed all of the substrate, Sanders said.

Using X-ray crystallography, Sanders was able to show the structure of the E. coli exopolyphosphatase and found the protein had a unique way of achieving its high processivity.

"There is a hole in the protein," he said. "This is extremely rare and provides a physical explanation of why it is so processive. The hole physically encompasses the substrate, keeping it in place, in addition to the usual chemical bonding that keeps it attached. Once the protein attaches to the substrate, it doesn't come off. The protein chews away until it reaches the end of the substrate chain."

Sanders worked with a team to create the first-of-its-kind animated movie showing this process from the point of view of the substrate. The audience follows along as it is pulled through the protein from one side to the next.

"This is the first time this sort of thing has ever been seen, and this is the first movie of its kind," he said. "It elegantly illustrates the physical process of this reaction."

Sanders also determined the structure of the protein and demonstrated that it belongs to the ASKHA (Acetate and Sugar Kinases, Hsp70, Actin) superfamily. Knowing the family to which a protein belongs allows researchers to use existing information about other members of the family to better understand the protein being studied. It also allows information gained from the study to be used for other members of the family, Sanders said.

"Fundamental basic research is the engine that drives the development of technology such as antibiotics," he said. "The next step in this research will be working to develop inhibitors for this protein and studying the applications to other bacteria."

This research was funded by the National Institutes of Health, David and Lucille Packard Foundation Fellowship, National Science Foundation Minority Fellowship, and NIH Institutional Training Award. The NIH-sponsored Cancer Center, part of Purdue's Oncological Sciences Center in Discovery Park also supported the research.

Mar. 31, 2015 — Using the assessment tool ForWarn, US Forest Service researchers can monitor the growth and development of vegetation that signals winter's end and the awakening of a new growing season. Now these ... full story

Mar. 31, 2015 — Until now electric fences and trenches have proved to be the most effective way of protecting farms and villages from night time raids by hungry elephants. But researchers think they may have come up ... full story

Mar. 31, 2015 — Researchers have detected a human fingerprint deep in the Borneo rainforest in Southeast Asia. Cold winds blowing from the north carry industrial pollutants from East Asia to the equator, with ... full story

Mar. 31, 2015 — A team of engineers and biologists reports new progress in using computer modeling and 3D shape analysis to understand how the unique grasping tails of seahorses evolved. These prehensile tails ... full story

Mar. 31, 2015 — As the five-year anniversary of the explosion of the Deepwater Horizon oil rig approaches, a new report looks at how twenty species of wildlife are faring in the aftermath of the ... full story

Mar. 31, 2015 — Scientists have uncovered the earliest fossilized evidence of an insect caring for its young. The findings push back the earliest direct evidence of insect brood care by more than 50 million years, ... full story

Mar. 31, 2015 — New research has scientists re-thinking how a lethal fungus grows and kills immune cells. The study hints at a new approach to therapy for Candida albicans, one of the most common causes of ... full story

Mar. 31, 2015 — The most virulent strains of Streptococcus suis, the leading cause of bacterial meningitis in adult humans in parts of southeast Asia and in pigs around the world, are likely to have evolved and ... full story

Mar. 31, 2015 — Darwin's evolutionary theory predicts survival of the fittest. So why do different survival tactics co-exist, if evolution should always favor the winning strategy? To answer that question scientists ... full story

Bionic Ants Could Be Tomorrow's Factory Workers

Reuters - Innovations Video Online (Mar. 30, 2015) — Industrious 3D printed bionic ants working together could toil in the factories of the future, says German technology company Festo. The robotic insects cooperate and coordinate their actions and movements to achieve a common aim. Amy Pollock reports.
Video provided by Reuters

Lions Make Surprise Comeback in Gabon

AFP (Mar. 30, 2015) — Lions have made a comeback in southeast Gabon, after disappearing for years, according to live footage from US wildlife organisation Panthera. Duration: 00:32
Video provided by AFP

Related Stories

Feb. 17, 2014 — Scientists have deciphered the 3-D structure of a protein that confers antibiotic resistance from one of the most worrisome disease agents: a strain of bacteria called methicillin-resistant ... full story

Nov. 15, 2012 — Researchers have found an unlikely recipe for antibiotic resistant bacteria: Mix cow dung and soil, and add urine infused with metabolized antibiotic. The urine will kill off normal E. coli in the ... full story

Dec. 7, 2011 — Water discharged into lakes and rivers from municipal sewage treatment plants may contain significant concentrations of the genes that make bacteria antibiotic-resistant. That's the conclusion ... full story

June 14, 2011 — E. coli bacteria exposed to three common antibiotics were more likely to develop antibiotic resistance following low-level antibiotic exposure than after exposure to high concentrations that would ... full story

Nov. 1, 2010 — Short courses of antibiotics can leave normal gut bacteria harbouring antibiotic resistance genes for up to two years after treatment, say scientists in a new study. The researchers believe that this ... full story

ScienceDaily features breaking news and videos about the latest discoveries in health, technology, the environment, and more -- from major news services and leading universities, scientific journals, and research organizations.